There is still much to be learned about the nature and secretory control of circulating parathyroid hormone (PTH) in disease. It is the purpose of this project to study the secretion, function, and mechanism of action of parathyroid hormone, its relationship to human disease, and to develop clinically useful tests for circulating parathyroid hormone. From these studies it is expected that one can understand the pathophysiology of certain metabolic diseases of bone and endocrine disturbances. The entire structures of bovine, porcine, rat and human parathyroid hormone have been determined. Synthetic polypeptides representing bovine rat and human parathyroid hormone have been synthesized. These molecules show all the biological properties of the native hormonal polypeptides. Highly sensitive radioimmunoassays for the hormone have been developed and are being modified further for improved clinical diagnostic parameters. Studies show that the mechanism of action of the hormone is mediated through direct hormonal activation of adenylate cyclase in bone and kidney. Isolated parathyroid cells and culture systems have been developed that allow studies on secretory control of parathyroid hormone, and provide test systems to elucidate the pathophysiology of certain hypoparathyroid and hyperparathyroid states.